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Development of the Enteric Neuromuscular System

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Pediatric Neurogastroenterology

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Abstract

In order for the gut to perform essential functions, including moving contents along its length via the organized movement of peristalsis, as well as absorption of water and electrolytes, secretion from glands, and regulation of blood flow, the integrated function of multiple tissues and cell types must occur. The mature, functioning neuromuscular system of the gut is composed of smooth muscle cells, neurons and glial cells of the enteric nervous system (ENS), and interstitial cells of Cajal (ICC). These diverse components arise from distinct sources during development, and must, during the course of embryogenesis, acquire appropriate integration to enable a functioning neuromuscular system to commence coordinated activity around birth. Here, we utilize information gleaned from studies in animal models such as mouse, chick, guinea pig, and zebrafish, as well as human studies, to describe the development of each constituent part of the neuromuscular system as well as to outline how these component parts become integrated into a functioning whole. Moreover, our discussions touch on diseases affecting development of the enteric neuromuscular system, notably Hirschsprung’s disease (HSCR), one of the most common gut motility disorders.

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References

  1. Roberts DJ. Molecular mechanisms of development of the gastrointestinal tract. Dev Dyn. 2000;219:109–20.

    Article  PubMed  CAS  Google Scholar 

  2. van den Brink GR. Hedgehog signaling in development and homeostasis of the gastrointestinal tract. Physiol Rev. 2007;87:1343–75.

    Article  PubMed  CAS  Google Scholar 

  3. Ramalho-Santos M, Melton DA, McMahon AP. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 2000;127:2763–72.

    PubMed  CAS  Google Scholar 

  4. Masumoto K, Nada O, Suita S, Taguchi T, Guo R. The formation of the chick ileal muscle layers as revealed by alpha-smooth muscle actin immunohistochemistry. Anat Embryol. 2000;201:121–9.

    Article  PubMed  CAS  Google Scholar 

  5. Gabella G. Development of visceral smooth muscle. Results Probl Cell Differ. 2002;38:1–37.

    Article  PubMed  Google Scholar 

  6. McHugh KM. Molecular analysis of smooth muscle development in the mouse. Dev Dyn. 1995;204:278–90.

    Article  PubMed  CAS  Google Scholar 

  7. Wallace AS, Burns AJ. Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract. Cell Tissue Res. 2005;319:367–82.

    Article  PubMed  Google Scholar 

  8. Gunst SJ, Zhang W. Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am J Physiol Cell Physiol. 2008;295:C576–87.

    Article  PubMed  CAS  Google Scholar 

  9. Burns AJ, Roberts RR, Bornstein JC, Young HM. Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages. Semin Pediatr Surg. 2009;18:196–205.

    Article  PubMed  Google Scholar 

  10. Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45:1–14.

    Article  PubMed  CAS  Google Scholar 

  11. Young HM, Newgreen D, Burns AJ. The Development of the enteric nervous system in relation to Hirschsprung’s disease. In: Ferretti P, Copp AJ, Tickle C, Moore G, editors. Embryos, genes and birth defects. 2nd ed. Chichester: John Wiley and Sons; 2006. p. 263–300.

    Google Scholar 

  12. Kenny SE, Tam PK, Garcia-Barcelo M. Hirschsprung’s disease. Semin Pediatr Surg. 2010;19:194–200.

    Article  PubMed  Google Scholar 

  13. Bealer JF, Natuzzi ES, Buscher C, et al. Nitric oxide synthase is deficient in the aganglionic colon of patients with Hirschsprung’s disease. Pediatrics. 1994;93:647–51.

    PubMed  CAS  Google Scholar 

  14. Larsson LT, Shen Z, Ekblad E, Sundler F, Alm P, Andersson KE. Lack of neuronal nitric oxide synthase in nerve fibers of aganglionic intestine: a clue to Hirschsprung’s disease. J Pediatr Gastroenterol Nutr. 1995;20:49–53.

    Article  PubMed  CAS  Google Scholar 

  15. Yamataka A, Miyano T, Okazaki T, Nishiye H. Correlation between extrinsic nerve fibers and synapses in the muscle layers of bowels affected by Hirschsprung’s disease. J Pediatric Surg. 1992;27:1213–6.

    Article  CAS  Google Scholar 

  16. Tennyson VM, Pham TD, Rothman TP, Gershon MD. Abnormalities of smooth muscle, basal laminae, and nerves in the aganglionic segments of the bowel of lethal spotted mutant mice. Anat Rec. 1986;215:267–81.

    Article  PubMed  CAS  Google Scholar 

  17. Hillemeier C, Biancani P. Mechanical properties of obstructed colon in a Hirschsprung’s model. Gastroenterology. 1990;99:995–1000.

    PubMed  CAS  Google Scholar 

  18. Won KJ, Torihashi S, Mitsui-Saito M, et al. Increased smooth muscle contractility of intestine in the genetic null of the endothelin ETB receptor: a rat model for long segment Hirschsprung’s disease. Gut. 2002;50:355–60.

    Article  PubMed  CAS  Google Scholar 

  19. Barlow AJ, Wallace AS, Thapar N, Burns AJ. Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation. Development. 2008;135:1681–91.

    Article  PubMed  CAS  Google Scholar 

  20. Lecoin L, Gabella G, Le Douarin N. Origin of the c-kit-positive interstitial cells in the avian bowel. Development. 1996;122:725–33.

    PubMed  CAS  Google Scholar 

  21. Antonucci A, Fronzoni L, Cogliandro L, et al. Chronic intestinal pseudo-obstruction. World J Gastroenterol. 2008;14:2953–61.

    Article  PubMed  CAS  Google Scholar 

  22. Mao J, Kim BM, Rajurkar M, Shivdasani RA, McMahon AP. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development. 2010;137:1721–9.

    Article  PubMed  CAS  Google Scholar 

  23. Furness JB. The enteric nervous system. Oxford: Blackwell Publishing; 2006.

    Google Scholar 

  24. Furness JB, Jones C, Nurgali K, Clerc N. Intrinsic primary afferent neurons and nerve circuits within the intestine. Prog Neurobiol. 2004;72:143–64.

    Article  PubMed  CAS  Google Scholar 

  25. Powley TL. Vagal input to the enteric nervous system. Gut. 2000;47 Suppl 4:iv30–2. discussion iv36.

    PubMed  Google Scholar 

  26. Gabella G. The number of neurons in the small intestine of mice, guinea-pigs and sheep. Neuroscience. 1987;22:737–52.

    Article  PubMed  CAS  Google Scholar 

  27. Hao MM, Young HM. Development of enteric neuron diversity. J Cell Mol Med. 2009;13:1193–210.

    Article  PubMed  CAS  Google Scholar 

  28. Gershon MD, Chalazonitis A, Rothman TP. From neural crest to bowel: development of the enteric nervous system. J Neurobiol. 1993;24:199–214.

    Article  PubMed  CAS  Google Scholar 

  29. Ruhl A. Glial cells in the gut. Neurogastroenterol Motil. 2005;17:777–90.

    Article  PubMed  CAS  Google Scholar 

  30. Blaugrund E, Pham TD, Tennyson VM, et al. Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence. Development. 1996;122:309–20.

    PubMed  CAS  Google Scholar 

  31. Durbec PL, Larsson-Blomberg LB, Schuchardt A, Costantini F, Pachnis V. Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. Development. 1996;122:349–58.

    PubMed  CAS  Google Scholar 

  32. Anderson RB, Stewart AL, Young HM. Phenotypes of neural-crest-derived cells in vagal and sacral pathways. Cell Tissue Res. 2006;323:11–25.

    Article  PubMed  CAS  Google Scholar 

  33. Burns AJ, Champeval D, Le Douarin NM. Sacral neural crest cells colonise aganglionic hindgut in vivo but fail to compensate for lack of enteric ganglia. Dev Biol. 2000;219:30–43.

    Article  PubMed  CAS  Google Scholar 

  34. Burns AJ, Le Douarin NM. The sacral neural crest contributes neurons and glia to the post-umbilical gut: spatiotemporal analysis of the development of the enteric nervous system. Development. 1998;125:4335–47.

    PubMed  CAS  Google Scholar 

  35. McKeown SJ, Chow CW, Young HM. Development of the submucous plexus in the large intestine of the mouse. Cell Tissue Res. 2001;303:301–5.

    Article  PubMed  CAS  Google Scholar 

  36. Druckenbrod NR, Epstein ML. The pattern of neural crest advance in the cecum and colon. Dev Biol. 2005;287:125–33.

    Article  PubMed  CAS  Google Scholar 

  37. Druckenbrod NR, Epstein ML. Behavior of enteric neural crest-derived cells varies with respect to the migratory wavefront. Dev Dyn. 2007;236:84–92.

    Article  PubMed  Google Scholar 

  38. Young HM, Bergner AJ, Anderson RB, et al. Dynamics of neural crest-derived cell migration in the embryonic mouse gut. Dev Biol. 2004;270:455–73.

    Article  PubMed  CAS  Google Scholar 

  39. Hao MM, Anderson RB, Kobayashi K, Whitington PM, Young HM. The migratory behavior of immature enteric neurons. Dev Neurobiol. 2009;69:22–35.

    Article  PubMed  CAS  Google Scholar 

  40. Manie S, Santoro M, Fusco A, Billaud M. The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet. 2001;17:580–9.

    Article  PubMed  CAS  Google Scholar 

  41. Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature. 1994;367:380–3.

    Article  PubMed  CAS  Google Scholar 

  42. Tam PK, Garcia-Barcelo M. Genetic basis of Hirschsprung’s disease. Pediatr Surg Int. 2009;25:543–58.

    Article  PubMed  Google Scholar 

  43. Lantieri F, Griseri P, Ceccherini I. Molecular mechanisms of RET-induced Hirschsprung pathogenesis. Ann Med. 2006;38:11–9.

    Article  PubMed  CAS  Google Scholar 

  44. Young HM, Hearn CJ, Farlie PG, Canty AJ, Thomas PQ, Newgreen DF. GDNF is a chemoattractant for enteric neural cells. Dev Biol. 2001;229:503–16.

    Article  PubMed  CAS  Google Scholar 

  45. Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev. 2007;8:466–79.

    Article  CAS  Google Scholar 

  46. Gershon MD. Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci. 2010;33:446–56.

    Article  PubMed  CAS  Google Scholar 

  47. Young HM, Turner KN, Bergner AJ. The location and phenotype of proliferating neural-crest-derived cells in the developing mouse gut. Cell Tissue Res. 2005;320:1–9.

    Article  PubMed  CAS  Google Scholar 

  48. Stanchina L, Baral V, Robert F, et al. Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development. Dev Biol. 2006;295:232–49.

    Article  PubMed  CAS  Google Scholar 

  49. Gianino S, Grider JR, Cresswell J, Enomoto H, Heuckeroth RO. GDNF availability determines enteric neuron number by controlling precursor proliferation. Development. 2003;130:2187–98.

    Article  PubMed  CAS  Google Scholar 

  50. Simpson MJ, Zhang DC, Mariani M, Landman KA, Newgreen DF. Cell proliferation drives neural crest cell invasion of the intestine. Dev Biol. 2007;302:553–68.

    Article  PubMed  CAS  Google Scholar 

  51. Heuckeroth RO, Lampe PA, Johnson EM, Milbrandt J. Neurturin and GDNF promote proliferation and survival of enteric neuron and glial progenitors in vitro. Dev Biol. 1998;200:116–29.

    Article  PubMed  CAS  Google Scholar 

  52. Hearn CJ, Murphy M, Newgreen D. GDNF and ET-3 differentially modulate the numbers of avian enteric neural crest cells and enteric neurons in vitro. Dev Biol. 1998;197:93–105.

    Article  PubMed  CAS  Google Scholar 

  53. Barlow A, de Graaff E, Pachnis V. Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron. 2003;40:905–16.

    Article  PubMed  CAS  Google Scholar 

  54. Nagy N, Goldstein AM. Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system. Dev Biol. 2006;293(1):203–17.

    Article  PubMed  CAS  Google Scholar 

  55. Ngan ES, Shum CK, Poon HC, et al. Prokineticin-1 (Prok-1) works coordinately with glial cell line-derived neurotrophic factor (GDNF) to mediate proliferation and differentiation of enteric neural crest cells. Biochim Biophys Acta. 2008;1783:467–78.

    Article  PubMed  CAS  Google Scholar 

  56. Sato Y, Heuckeroth RO. Retinoic acid regulates murine enteric nervous system precursor proliferation, enhances neuronal precursor differentiation, and reduces neurite growth in vitro. Dev Biol. 2008;320:185–98.

    Article  PubMed  CAS  Google Scholar 

  57. Rothman TP, Sherman D, Cochard P, Gershon MD. Development of the monoaminergic innervation of the avian gut: transient and permanent expression of phenotypic markers. Dev Biol. 1986;116:357–80.

    Article  PubMed  CAS  Google Scholar 

  58. Sang Q, Young HM. The identification and chemical coding of cholinergic neurons in the small and large intestine of the mouse. Anat Rec. 1998;251:185–99.

    Article  PubMed  CAS  Google Scholar 

  59. Young HM, Bergner AJ, Muller T. Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine. J Comp Neurol. 2003;456:1–11.

    Article  PubMed  Google Scholar 

  60. Baetge G, Gershon MD. Transient catecholaminergic (TC) cells in the vagus nerves and bowel of fetal mice: relationship to the development of enteric neurons. Dev Biol. 1989;132:189–211.

    Article  PubMed  CAS  Google Scholar 

  61. Young HM, Ciampoli D, Hsuan J, Canty AJ. Expression of Ret-, p75(NTR)-, Phox2a-, Phox2b-, and tyrosine hydroxylase-immunoreactivity by undifferentiated neural crest-derived cells and different classes of enteric neurons in the embryonic mouse gut. Dev Dyn. 1999;216:137–52.

    Article  PubMed  CAS  Google Scholar 

  62. Pham TD, Gershon MD, Rothman TP. Time of origin of neurons in the murine enteric nervous system: sequence in relation to phenotype. J Comp Neurol. 1991;314:789–98.

    Article  PubMed  CAS  Google Scholar 

  63. Rothman TP, Tennyson VM, Gershon MD. Colonization of the bowel by the precursors of enteric glia: studies of normal and congenitally aganglionic mutant mice. J Comp Neurol. 1986;252:493–506.

    Article  PubMed  CAS  Google Scholar 

  64. Hendershot TJ, Liu H, Sarkar AA, et al. Expression of Hand2 is sufficient for neurogenesis and cell type-specific gene expression in the enteric nervous system. Dev Dyn. 2007;236:93–105.

    Article  PubMed  CAS  Google Scholar 

  65. D’Autreaux F, Morikawa Y, Cserjesi P, Gershon MD. Hand2 is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia. Development. 2007;134:2237–49.

    Article  PubMed  CAS  Google Scholar 

  66. Hens J, Vanderwinden JM, De Laet MH, Scheuermann DW, Timmermans JP. Morphological and neurochemical identification of enteric neurones with mucosal projections in the human small intestine. J Neurochem. 2001;76:464–71.

    Article  PubMed  CAS  Google Scholar 

  67. Porter AJ, Wattchow DA, Brookes SJ, Costa M. The neurochemical coding and projections of circular muscle motor neurons in the human colon. Gastroenterology. 1997;113:1916–23.

    Article  PubMed  CAS  Google Scholar 

  68. Wattchow DA, Porter AJ, Brookes SJ, Costa M. The polarity of neurochemically defined myenteric neurons in the human colon. Gastroenterology. 1997;113:497–506.

    Article  PubMed  CAS  Google Scholar 

  69. Hofstra RM, Landsvater RM, Ceccherini I, et al. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature. 1994;367:375–6.

    Article  PubMed  CAS  Google Scholar 

  70. Meier-Ruge WA, Bruder E, Kapur RP. Intestinal neuronal dysplasia type B: one giant ganglion is not good enough. Pediatr Dev Pathol. 2006;9:444–52.

    Article  PubMed  Google Scholar 

  71. Shirasawa S, Yunker AM, Roth KA, Brown GA, Horning S, Korsmeyer SJ. Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon. Nature Med. 1997;3:646–50.

    Article  PubMed  CAS  Google Scholar 

  72. Dingemann J, Puri P. Isolated hypoganglionosis: systematic review of a rare intestinal innervation defect. Pediatr Surg Int. 2010;26:1111–5.

    Article  PubMed  Google Scholar 

  73. Gershon MD. The enteric nervous system: a second brain. Hosp Pract (Off Ed). 1999;34:31–2. 35–38, 41–32 passim.

    Article  CAS  Google Scholar 

  74. Shen L, Pichel JG, Mayeli T, Sariola H, Lu B, Westphal H. Gdnf haploinsufficiency causes Hirschsprung-like intestinal obstruction and early-onset lethality in mice. Am J Hum Genet. 2002;70:435–47.

    Article  PubMed  CAS  Google Scholar 

  75. Carniti C, Belluco S, Riccardi E, et al. The Ret(C620R) mutation affects renal and enteric development in a mouse model of Hirschsprung’s disease. Am J Pathol. 2006;168:1262–75.

    Article  PubMed  CAS  Google Scholar 

  76. Young HM, Jones BR, McKeown SJ. The projections of early enteric neurons are influenced by the direction of neural crest cell migration. J Neurosci. 2002;22:6005–18.

    PubMed  CAS  Google Scholar 

  77. Olden T, Akhtar T, Beckman SA, Wallace KN. Differentiation of the zebrafish enteric nervous system and intestinal smooth muscle. Genesis. 2008;46:484–98.

    Article  PubMed  Google Scholar 

  78. Heanue TA, Pachnis V. Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes. PNAS 2006;103:6919–24.

    Article  PubMed  CAS  Google Scholar 

  79. Vannucchi MG, Faussone-Pellegrini MS. Synapse formation during neuron differentiation: an in situ study of the myenteric plexus during murine embryonic life. J Comp Neurol. 2000;425:369–81.

    Article  PubMed  CAS  Google Scholar 

  80. Vohra BP, Tsuji K, Nagashimada M, et al. Differential gene expression and functional analysis implicate novel mechanisms in enteric nervous system precursor migration and neuritogenesis. Dev Biol. 2006;298:259–71.

    Article  PubMed  CAS  Google Scholar 

  81. Maeda H, Yamagata A, Nishikawa S, et al. Requirement of c-kit for development of intestinal pacemaker system. Development. 1992;116:369–75.

    PubMed  CAS  Google Scholar 

  82. Burns AJ, Herbert TM, Ward SM, Sanders KM. Interstitial cells of Cajal in the guinea-pig gastrointestinal tract as revealed by c-Kit immunohistochemistry. Cell Tissue Res. 1997;290:11–20.

    Article  PubMed  CAS  Google Scholar 

  83. Vanderwinden JM, Rumessen JJ. Interstitial cells of Cajal in human gut and gastrointestinal disease. Microsc Res Tech. 1999;47:344–60.

    Article  PubMed  CAS  Google Scholar 

  84. Rumessen JJ, Vanderwinden JM. Interstitial cells in the musculature of the gastrointestinal tract: Cajal and beyond. Int Rev Cytol. 2003;229:115–208.

    Article  PubMed  CAS  Google Scholar 

  85. Torihashi S, Ward SM, Nishikawa S, Nishi K, Kobayashi S, Sanders KM. c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res. 1995;280:97–111.

    PubMed  CAS  Google Scholar 

  86. Ward SM, Burns AJ, Torihashi S, Sanders KM. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994;480:91–7.

    PubMed  CAS  Google Scholar 

  87. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373:347–9.

    Article  PubMed  CAS  Google Scholar 

  88. Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. PNAS 1996;93:12008–13.

    Article  PubMed  CAS  Google Scholar 

  89. Ward SM, McLaren GJ, Sanders KM. Interstitial cells of Cajal in the deep muscular plexus mediate enteric motor neurotransmission in the mouse small intestine. J Physiol. 2006;573:147–59.

    Article  PubMed  CAS  Google Scholar 

  90. Young HM, Ciampoli D, Southwell BR, Newgreen DF. Origin of interstitial cells of Cajal in the mouse intestine. Dev Biol. 1996;180:97–107.

    Article  PubMed  CAS  Google Scholar 

  91. Kenny SE, Connell G, Woodward MN, et al. Ontogeny of interstitial cells of Cajal in the human intestine. J Pediatr Surg. 1999;34:1241–7.

    Article  PubMed  CAS  Google Scholar 

  92. Wester T, Eriksson L, Olsson Y, Olsen L. Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry. Gut. 1999;44:65–71.

    Article  PubMed  CAS  Google Scholar 

  93. Wu JJ, Rothman TP, Gershon MD. Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand. J Neurosci Res. 2000;59:384–401.

    Article  PubMed  CAS  Google Scholar 

  94. Sanders KM, Ordog T, Ward SM. Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside. IV. Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol. 2002;282:G747–56.

    PubMed  CAS  Google Scholar 

  95. Burns AJ. Disorders of interstitial cells of Cajal. J Pediatr Gastroenterol Nutr. 2007;45 Suppl 2:S103–6.

    Article  PubMed  Google Scholar 

  96. Torihashi S, Nishi K, Tokutomi Y, Nishi T, Ward S, Sanders KM. Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype. Gastroenterology. 1999;117:140–8.

    Article  PubMed  CAS  Google Scholar 

  97. Sanders KM, Ordog T, Koh SD, Torihashi S, Ward SM. Development and plasticity of interstitial cells of Cajal. Neurogastroenterol Motil. 1999;11:311–38.

    Article  PubMed  CAS  Google Scholar 

  98. Faussone-Pellegrini MS, Vannucchi MG, Ledder O, Huang TY, Hanani M. Plasticity of interstitial cells of Cajal: a study of mouse colon. Cell Tissue Res. 2006;325(2):211–7.

    Article  PubMed  Google Scholar 

  99. Huizinga JD, Zarate N, Farrugia G. Physiology, injury, and recovery of interstitial cells of Cajal: basic and clinical science. Gastroenterology. 2009;137:1548–56.

    Article  PubMed  Google Scholar 

  100. Yamataka A, Kato Y, Tibboel D, et al. A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung’s disease. J Pediatric Surg. 1995;30:441–4.

    Article  CAS  Google Scholar 

  101. Vanderwinden JM, Rumessen JJ, Liu H, Descamps D, De Laet MH, Vanderhaeghen JJ. Interstitial cells of Cajal in human colon and in Hirschsprung’s disease. Gastroenterology. 1996;111:901–10.

    Article  PubMed  CAS  Google Scholar 

  102. Horisawa M, Watanabe Y, Torihashi S. Distribution of c-Kit immunopositive cells in normal human colon and in Hirschsprung’s disease. J Pediatric Surg. 1998;33:1209–14.

    Article  CAS  Google Scholar 

  103. Newman CJ, Laurini RN, Lesbros Y, Reinberg O, Meyrat BJ. Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung’s disease. Pediatric Surg Int. 2003;19:662–8.

    Article  CAS  Google Scholar 

  104. Ward SM, Ordog T, Bayguinov JR, et al. Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves. Gastroenterology. 1999;117:584–94.

    Article  PubMed  CAS  Google Scholar 

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Heanue, T.A., Burns, A.J. (2013). Development of the Enteric Neuromuscular System. In: Faure, C., Di Lorenzo, C., Thapar, N. (eds) Pediatric Neurogastroenterology. Clinical Gastroenterology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-709-9_2

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